Lysed hemoglobin breaks down into alpha-beta dimers, which are small (MW: 34k) and cleared via glomerular filtration by the kidney -> resulting in hemoglobinuria

Hemoglobin dimers filtered by the kidney are taken up by renal tubular cells, degraded, and the iron stored as hemosiderin -> when renal tubular cells are later sloughed into the urine (approximately 7 days later), hemosiderinuria can be detected (by the Prussian blue reaction)

Autoimmune Hemolytic Anemia (AIHA): may occur in some cases (where IgM forms an antibody-antigen complex on the RBC membrane -> activation of complement with RBC lysis)

Extravascular Hemolysis (RBC Destruction in the Spleen, Other Reticuloendothelial Tissues, or Extravasated Blood/Hematoma)

General Comments

Hepatic Destruction of RBC’s: primary site of destruction of severely damaged RBC’s (especially those coated with complement)

Liver receives larger percentage of cardiac output than the spleen

Splenic Destruction of RBC’s: primary site of destruction of poorly-deformable RBC’s (spherocytes, etc), due to narrow passage in the cords of Billroth -> macrophage ingestion of RBC’s (with degradation of hemoglobin to iron/biliverdin/carbon monoxide)

Biliverdin is converted to unconjugated bilirubin, which is released into the plasma

Physiology: with intravascular hemolysis, hemoglobin is released from hemolyzed RBC’s into the blood, exceeding the binding capacity of haptoglobin -> excess hemoglobin is filtered by the kidney

Some of this hemoglobin is excreted in the urine, resulting in hemoglobinuria (with “coca cola-colored” urine)

Some of this hemoglobin is reabsorbed in the proximal convoluted tubule, where the iron portion is removed and stored in ferritin or hemosiderin -> proximal tubule cells slough off (containing the hemosiderin) and are excreted into the urine, resulting in hemosiderinuria

Urine hemosiderin (composed of a complex of ferritin, denatured ferritin, and other material) can be detected in iron-stained urinary sediment (within the sloughed proximal tubular cells)

Diagnostic Utility

Urine hemoglobin disappears more quickly from the urine than hemosiderin, making it less sensitive for the presence of hemolysis (especially in cases with intermittent hemolysis)

Urine Hemosiderin can remain in the urine for several weeks (making it a more sensitive marker for hemolysis in the recent past): however, after an acute episode of intravascular hemolysis, several days may pass before urinary hemosiderin can be detected